Regulation of interleukin-8 expression by cellular pH in human pancreatic adenocarcinoma cells

The role of cellular pH in the expression and regulation of interleukin-8 ( IL-8) in human tumor cell lines was determined. Transient exposure to pH ra nging from 7.4 to 6.7 induced pH-dependent expression of IL-8 at both the m RNA and protein levels in three different human tumor cell lines, including COLO357 pancreatic adenocarcinoma cells, SW620 colon adenocarcinoma cells, and PC3 prostate adenocarcinoma cells. Investigation of the mechanisms of IL-8 induction in response to acidosis was carried out using the COLO357 hu man pancreatic cancer cell line. The increased steady-state level of mRNA c orrelated with an increased transcription rate and stability of IL-8 transc ripts. Further experiments indicated that mild acidosis activated the trans cription factors NF-kappaB and AP-1 and that the cooperation of these two f actors appeared to be essential to the transactivation of the IL-8 gene. Ou r data demonstrated that low tumor pH contributes to the enhanced expressio n of IL-8 and plays an important role in tumor progression.